Genetic Risk of Heart Failure and its Subphenotypes

Coordinator:		Prof. Dr. Hugo A. Katus                                                                              Prof. Dr. Burkert Pieske, Prof. Dr. Gerd Hasenfuß, PD Dr. Stefan Kääb
Institution:		Abteilung Innere Medizin III, Uniklink Heidelberg                          Abteilung Kardiologie und Pneumologie, Herzzentrum Göttingen  Medizinische Klinik und Poliklinik I, LMU München
Homepage:		www.klinikum.uni-heidelberg.de

The initiative within the Program of Medical Genome Research „Genetics of Heart Failure“ comprises of 13 subprojects. The core subproject is the clinically oriented subproject 1. This subproject is based on results which have been worked out in the NGFN-2 “GWAS consortium”. This consortium performed genome wide analyses of more than 20 important disease entities with each 500 cases (of these 4 cardiovascular phenotpyes: Dilated Cardiomyopathy (DCM), Left Ventricular Hypertrophy (LVH), Diastolic Dysfunction (DD) and Atrial fibrillation (AF) as well as control cohorts of two independent population based platforms KORA-gen (Augsburg / Munich) and popgen (Kiel). In subproject 1 the results of the initially analyzed 2.000 patients shall be confirmed by analyses of additional 1.000 clinically excellent characterized patients per subphenotype. Control cohorts of at least 2.000 persons where recruited from the KORA-gen and popgen platforms. From these confirmation analyses a number of polymorphic markers (SNP`s), candidate genes or candidate regions, respectively, will be expected which have been already significant in the primary analysis or which will first reach genome wide significance level (p=10-6) under these conditions. In cooperation with other subprojects of this initiative these candidate genes or – regions will be investigated functionally in detail (in vitro and in animal models). In a further work package clinical progression and the clinical end point of all these 4.000 patients (1.000 per subphenotpye) will be anlyzed 5 years post inclusion. Moreover those SNP`s which reached genome wide significance level in all subphenotpyes will be investigated clinically prospective. To do this a subgroup of 3.000 patients with symptomatic Heart Failure will be clinically followed over 3 years and genotpyed with respect to the most robust risk markers. By utilizing clinical and genomic data predictive markers for Heart Failure risk or Heart Failure progression, respectively, shall be determined.